If functional abnormalities are detected, human genetic studies will be done to determine if the abnormality is inheritable and/or molecular biology techniques will be used to specifically identify the abnormality. Using this approach, it can be determined if a genetic discriminant or variation is genetically involved in the psychiatric illness. The applicants initial research project will focus on evaluating the content and functioning of G proteins in the peripheral blood cells of patients with primary mood disorders, and the effects of lithium on these measures. Receptor binding studies and G protein activation of the enzymes adenylate cyclase and phospholipase C, will be used to assess the functional activity of the G proteins.Quantitation of the subtypes of G proteins will be done by ELISA using commercially available antibodies. If a discriminant variable is detected in the probands, human genetic studies and/or molecular biology assessments will be done.